A Study of GDC-0853 in Participants With Refractory Chronic Spontaneous Urticaria (CSU).

A Phase II, Multicenter, Randomized, Double-Blind, Placebo-Controlled Pilot and Dose-Ranging Study of GDC-0853 in Patients With Refractory Chronic Spontaneous Urticaria (CSU).

The purpose of this study is to evaluate the efficacy, safety and pharmacokinetics of GDC-0853 compared with placebo in participants with Refractory Chronic Spontaneous Urticaria (CSU) already treated with anti-histamines. Participants have the option to enter the Open-Label Extension (OLE) study after completing the 8-week treatment period.

Study Overview

• Status: Completed
• Conditions: Urticaria
• Intervention / Treatment: Drug: Placebo; Drug: GDC-0853

• Study Type: Interventional
• Enrollment (Actual): 134
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V6T 1Z4
      • University of British Columbia
  • Ontario
    • Hamilton, Ontario, Canada, L8S 1G5
      • Private Practice - Dr. Jason Ohayon
    • Markham, Ontario, Canada, L3P 1X2
      • Lynde Institute for Dermatology
    • Mississauga, Ontario, Canada, L5A 3V4
      • Cheema Research
    • Ottawa, Ontario, Canada, K1G 6C6
      • Yang Medicine
    • Toronto, Ontario, Canada, M4V 1R2
      • Gordon Sussman Clinical Research
  • Quebec
    • Drummondville, Quebec, Canada, J2B 5L4
      • Private Practice - Dr. Isabelle Delorme
    • Quebec City, Quebec, Canada, G1V 4M6
      • Centre de Recherche Appliqué en Allergie de Québec
• Germany
  • Augsburg, Germany, 86179
    • Licca Clinical Research Institute
  • Berlin, Germany, 10117
    • Charite Mitte; Klinik fur Dermatologie
  • Dresden, Germany, 01307
    • Universitätsklinikum Carl Gustav Carus, Klinik und Poliklinik für Augenheilkunde
  • Mahlow, Germany, 15831
    • Hautarztpraxis Mahlow
  • Mainz, Germany, 55131
    • Universitätsmedizin Johannes Gutenberg Universität
  • Münster, Germany, 48419
    • Klinik für Haut- und Geschlechtskrankheiten, Universitätsklinikum Münster
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35209
      • Clinical Research Center of Alabama, LLC
  • Arizona
    • Scottsdale, Arizona, United States, 85251
      • Allergy & Asthma Immunology Associates
  • California
    • Bakersfield, California, United States, 93301
      • Kern Allergy Med Clinic, Inc.
    • Mission Viejo, California, United States, 92691
      • Southern California Research Center
    • Redwood City, California, United States, 94063
      • Allergy & Asthma Consultants
    • Riverside, California, United States, 92506
      • Integrated Research Group Inc
    • Upland, California, United States, 91786
      • Integrated Research of Inland
  • Florida
    • Miami, Florida, United States, 33165
      • New Horizon Research Center
    • Ocala, Florida, United States, 34470
      • Renstar Medical Research
  • Oklahoma
    • Tulsa, Oklahoma, United States, 74136
      • Vital Prospects Clinical Research Institute PC - CRN
  • Rhode Island
    • East Providence, Rhode Island, United States, 02914
      • Asthma, Nasal Disease, and Allergy Research Center of New England
  • Texas
    • Cypress, Texas, United States, 77433
      • Center for Clinical Studies
  • Vermont
    • Burlington, Vermont, United States, 05403
      • Timber Lane Allergy and Asthma Research, LLC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Aged 18-75 years, inclusive
• Diagnosis of chronic spontaneous urticaria (CSU) refractory to H1 antihistamines at the time of randomization
• Willing and able to complete an Urticaria Participant Daily eDiary for the duration of the study
• No evidence of active or latent or inadequately treated infection with tuberculosis (TB)
• Partcipants with a history of Bacille Calmette-Guérin (BCG) vaccination should be screened using the QuantiFERON-TB-Gold (QFT) test
• Only for participants currently receiving proton-pump inhibitors (PPIs) or H2 receptor antagonists (H2RAs): Treatment must be at a stable dose during the 2-week screening period prior to randomization and with a plan to remain at a stable dose for the duration of the study
• For women of childbearing potential: Agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods that result in a failure rate of <1% per year during the treatment period and for at least 4 weeks after the last dose of study drug. Women must refrain from donating eggs during this same period.

Exclusion Criteria:

• Treatment with omalizumab or other monoclonal antibody therapies used to treat CSU within 4 months prior to screening or primary nonresponse to omalizumab
• Use of a non-biologic investigational drug or participation in an investigational study with a non-biologic drug within 30 days prior to study drug administration on Day 1 (or within 5 half-lives of the investigational product, whichever is greater)
• Use of a biologic investigational therapy or participation in an investigational study involving biologic therapy within 90 days or 5 half-lives, whichever is greater, prior to study drug administration on Day 1
• Previous treatment with GDC-0853 or other Bruton's tyrosine kinase (BTK) inhibitors
• Participants whose urticaria is solely due to physical urticaria
• Other diseases with symptoms of urticaria or angioedema, including urticarial vasculitis, urticaria pigmentosa, erythema multiforme, mastocytosis, hereditary or acquired angioedema, lymphoma, or leukemia
• Atopic dermatitis, bullous pemphigoid, dermatitis herpetiformis, or other skin disease associated with itch such as psoriasis
• Routine doses of the following medications within 30 days prior to screening: systemic or cutaneous (topical) corticosteroids (prescription or over the counter), hydroxychloroquine, methotrexate, cyclosporine, or cyclophosphamide
• Prior utilization of intravenous (IV) steroids for treatment of laryngeal angioedema
• Intravenous immunoglobulin G (IV IG) or plasmapheresis within 30 days prior to screening
• History of anaphylactic shock without clearly identifiable avoidable antigen
• Hypersensitivity to GDC-0853 or any component of the formulation
• Major surgery within 8 weeks prior to screening or surgery planned prior to end of study (12 weeks after randomization)
• Require any prohibited concomitant medications
• History of live attenuated vaccine within 6 weeks prior to randomization or requirement to receive these vaccinations at any time during study drug treatment
• Evidence of clinically significant cardiac, neurologic, psychiatric, pulmonary, renal, hepatic, endocrine, metabolic, or gastrointestinal (GI) disease that, in the investigator's opinion, would compromise the safety of the participant, interfere with the interpretation of the study results or otherwise preclude participant participation
• Current treatment with astemizole, terfenadine, and/or ebastine
• Uncontrolled disease states, such as asthma, psoriasis, or inflammatory bowel disease, where flares are commonly treated with oral or parenteral corticosteroids

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Cohort 1: Placebo; Participants received matching placebo twice daily from Day 1 to 56.	Drug: Placebo; Matching Placebo will be administered orally, as per the dosing schedules described above.
EXPERIMENTAL: Cohort 1: GDC-0853 200mg BID; Participants received GDC-0853 200mg twice daily from Day 1 to 56.	Drug: GDC-0853; GDC-0853 will be administered orally at dosages of 50, 150 and 200mg to participants, as per the dosing schedules described above.
PLACEBO_COMPARATOR: Cohort 2: Placebo; Participants received matching placebo up to twice daily from Day 1 to 56.	Drug: Placebo; Matching Placebo will be administered orally, as per the dosing schedules described above.
EXPERIMENTAL: Cohort 2: GDC-0853 50mg QD; Participants received GDC-0853 50mg once daily from Day 1 to 56.	Drug: GDC-0853; GDC-0853 will be administered orally at dosages of 50, 150 and 200mg to participants, as per the dosing schedules described above.
EXPERIMENTAL: Cohort 2: GDC-0853 150mg QD; Participants received GDC-0853 150mg once daily from Day 1 to 56.	Drug: GDC-0853; GDC-0853 will be administered orally at dosages of 50, 150 and 200mg to participants, as per the dosing schedules described above.
EXPERIMENTAL: Cohort 2: GDC-0853 200mg BID; Participants received GDC-0853 200mg twice daily from Day 1 to 56.	Drug: GDC-0853; GDC-0853 will be administered orally at dosages of 50, 150 and 200mg to participants, as per the dosing schedules described above.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in the Urticaria Activity Score Over 7 Days (UAS7) at Day 57	The Urticaria Activity Score (UAS) is a composite, diary-recorded score with numeric severity intensity ratings (0=none to 3=intense/severe) for the number of wheals (hives) and the intensity of the pruritus (itch) over the past 12 hours (twice daily). The daily UAS is calculated as the average of the morning and evening scores. The UAS7 is the weekly sum of the daily UAS, which is the composite score of the intensity of pruritus and the number of wheals. The maximum UAS7 value is 42. A higher score indicates worse disease. A negative change score (Day 57 score minus Baseline score) indicates improvement.	Baseline and Day 57

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Who Are Well-Controlled (UAS7 ≤ 6)	The Urticaria Activity Score (UAS) is a composite, diary-recorded score with numeric severity intensity ratings (0=none to 3=intense/severe) for the number of wheals (hives) and the intensity of the pruritus (itch) over the past 12 hours (twice daily). The daily UAS is calculated as the average of the morning and evening scores. The UAS7 is the weekly sum of the daily UAS, which is the composite score of the intensity of pruritus and the number of wheals. The maximum UAS7 value is 42. A higher score indicates worse disease. Participants with UAS7 score ≤6 are considered well controlled.	Day 57
Change From Baseline in the UAS7 at Day 29	The Urticaria Activity Score (UAS) is a composite, diary-recorded score with numeric severity intensity ratings (0=none to 3=intense/severe) for the number of wheals (hives) and the intensity of the pruritus (itch) over the past 12 hours (twice daily). The daily UAS is calculated as the average of the morning and evening scores. The UAS7 is the weekly sum of the daily UAS, which is the composite score of the intensity of pruritus and the number of wheals. The maximum UAS7 value is 42. A higher score indicates worse disease. A negative change score (Day 29 score minus Baseline score) indicates improvement.	Baseline and Day 29
Percentage of Participants With Adverse Events (AEs)	An Adverse Event (AE) is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An Adverse Event can therefore be any unfavorable and unintended sign (including abnormal laboratory values or abnormal clinical test results), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as Adverse Events.	Baseline up until 4 weeks after the last dose of study drug (up to 2 years, 5 months).
Plasma Concentrations of Fenebrutinib (GDC-0853) at Specified Timepoints	Plasma Concentration Data for fenebrutinib (GDC-0853) will be tabulated and summarised by visits. Descriptive summary statistics for Arithmetic Mean and Standard Deviation will be presented. Please note that the Placebo Cohorts were not evaluated for this Outcome Measure.	Days 1, 8 and 57.

Collaborators and Investigators

• Sponsor: Genentech, Inc.

Study record dates

Study Major Dates

• Study Start (ACTUAL): May 26, 2017
• Primary Completion (ACTUAL): September 27, 2019
• Study Completion (ACTUAL): October 25, 2019

Study Registration Dates

• First Submitted: April 28, 2017
• First Submitted That Met QC Criteria: April 28, 2017
• First Posted (ACTUAL): May 2, 2017

Study Record Updates

• Last Update Posted (ACTUAL): September 29, 2020
• Last Update Submitted That Met QC Criteria: September 28, 2020
• Last Verified: September 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Immune System Diseases; Hypersensitivity, Immediate; Skin Diseases, Vascular; Hypersensitivity; Urticaria; Chronic Urticaria
• Other Study ID Numbers: GS39684; 2016-004624-35 (EUDRACT_NUMBER)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No